: Ensuring the safety and comfort of critically ill infants or children supported on mechanical ventilation is integral to the practice of pediatric critical care. Humane pediatric intensive care often includes sedation management. Although there are clear benefits in using sedation in pediatric patients who are unable to understand the imperative nature of critical care instrumentation and immobility, sedative use is associated with iatrogenic injury. Specifically, the medications used for sedation may depress spontaneous ventilation and prolong the duration of mechanical ventilation. Over time, drug tolerance develops and may precipitate iatrogenic withdrawal syndrome when sedation is no longer necessary. Prolonging the duration of mechanical ventilation and iatrogenic withdrawal syndrome add to the personal and financial burden of intensive care. This cluster randomized clinical trial will test an innovative approach to sedation management that includes: [a] team education and consensus on the use of sedatives in pediatric patients supported on mechanical ventilation, [b] team identification of the patient's trajectory of illness and daily prescription of a sedation goal, [c] a Nurse-Implemented Goal-Directed Comfort Algorithm that guides moment-to-moment titration of opioids and benzodiazepines, and [d] team feedback on sedation management performance. The intervention is an organizational change directed at all PICU clinicians. The unit of randomization is the PICU, the unit of inference is the patient, and we will control for center effects. Eighteen pediatric intensive care units (9 randomized to the sedation management intervention and 9 to continue to provide usual care) will enroll 2754 critically-ill infants and children supported on mechanical ventilation. We believe that patients managed per sedation protocol will experience fewer days of mechanical ventilation, less sedative exposure, fewer iatrogenic withdrawal symptoms, a shorter intensive care length of stay, less costs, and experience a better post-discharge quality of life and emotional health.